Research from the Joyce Lab points to immunogenomic profiling as a means of maximizing efficacy of immunotherapies in lung and breast BrMs.
Brain metastases (BrMs) are the most frequent form of brain tumors and are associated with a very poor prognosis, highlighting the need for more effective therapies. Personalized medicine approaches guided by the genetic makeup of primary tumors are increasingly being used to improve therapy efficacy and immunotherapies are gaining momentum for the treatment of metastatic cancer. However, the immune microenvironment of BrMs is extremely heterogeneous and whether specific genomic alterations are associated with distinct immune states remains unknown.
To answer this question, the Joyce Lab and its collaborators, led by post-doctoral researcher Àngel Àlvarez-Prado, performed a multiparametric analysis of the immunogenomic landscape of human lung- and breast-BrMs by combining a range of diverse molecular profiling and imaging techniques.
The study*, published in Cell Reports Medicine, revealed that TP53 mutant lung-BrMs have a higher immune cell infiltration and display more activated CD8+ T cells and more immunosuppressive tumor-associated macrophages than their non-mutant counterparts. In breast-BrMs, researchers observed that hypermutation correlates with a higher proportion of infiltrating CD8+ T cells and an overall more inflamed immune microenvironment. These findings will enable the future development of personalized immunotherapies informed by the genomic profile of the tumors.
The research* was conducted in collaboration with the Lausanne University Hospital and the SIB Swiss Institute of Bioinformatics.
This project was supported by the Fondation ISREC, the Ludwig Institute for Cancer Research, the Breast Cancer Research Fund, the European Molecular Biology Organization and Marie Skłodowska-Curie Actions.
* Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors